Functional Characterization of Renal Tubular Epithelial Cells in Optimized Coculture Systems

Abstract

Background: Obtaining sufficient renal tubular epithelial cells (RTCs) and maintaining the functions of RTCs are vital for developing a bioartificial renal tubule-assisted device for continuous renal replacement therapy. Methods: We established an optimal Transwell coculture system using human primary renal proximal tubule epithelial cells (RPTECs) and bone marrow mesenchymal stem cells at different cell ratios to investigate morphological and functional changes in RTCs. Changes in cell proliferation, megalin expression, cell cycle, apoptosis, and levels of insulin-like growth factor-1 (IGF-1) and bone morphogenetic protein-7 (BMP-7) after cell culture were investigated. Results: RPTEC/BMMSC coculture at a cell ratio of 3:1 resulted in optimal morphology, function, and growth of RPTECs, in which, viability, proliferation, cytochrome P450 activity, and megalin expression in RPTECs were significantly increased compared to those in other cocultures or RPTECs alone. Additionally, IGF-1 and BMP-7 levels were significantly higher in the 3:1 RPTEC/BMMSC coculture than in the RPTECs alone. Conclusion: Our results demonstrate that coculture with RPTECs has great potential for use in renal replacement therapy, thereby providing fundamental information for manufacturing a bioartificial kidney.